Potassium bis(trimethylsilyl)amide → 5-[2-Benzyloxy-5-(4-ethylpiperazin-1-ylsulphonyl)pyridin-3-yl]-3-ethyl-2-(pyridin-2-yl)methyl-2,6-dihydro-7h-pyrazolo[4,3-d]pyrimidin-7-one

Potassium bis(trimethylsilyl)amide (360 mg, 1.81 mmol) was added to a stirred solution of the title compound of Example 1 (200 mg, 0.36 mmol) in benzyl alcohol (5 ml) at 100° C. and the reaction mixture stirred for 14 hours, then allowed to cool. The resulting mixture was partitioned between dichloromethane (10 ml) and brine (10 ml), the phases separated, the aqueous phase extracted with dichloromethane (2×10 ml) and the combined organic solutions dried (Na2SO4) and evaporated under reduced pressure. The residual benzyl alcohol was removed by Kugelrohr distillation, then the crude product purified by column chromatography on silica gel, using dichloromethane:methanol (97.5:2.5) as eluant, to provide the title compound (86 mg, 39%) as a white solid. Found: C, 59.92; H, 5.64; N, 17.60. C31H34N8O4S; 0.40H2O requires C, 59.87; H, 5.64; N, 18.02%. δ (CDCl3): 1.05 (3H, t), 1.29 (3H, t), 2.41 (2H, q), 2.56 (4H, m), 3.05 (2H, q), 3.15 (4H, m), 5.68 (2H, s), 5.75 (2H, s), 7.10 (1H, d), 7.24 (1H, m), 7.42 (3H, m), 7.52 (2H, m), 7.64 (1H, m), 8.58 (1H, d), 8.65 (1H, s), 9.02 (1H, s), 10.58 (1H, s). LRMS: m/z 615 (M+1)+.

1. temperatureto cool
2. customThe resulting mixture was partitioned between dichloromethane (10 ml) and brine (10 ml)
3. customthe phases separated
4. extractionthe aqueous phase extracted with dichloromethane (2×10 ml)
5. dry with materialthe combined organic solutions dried (Na2SO4)
6. customevaporated under reduced pressure
7. customThe residual benzyl alcohol was removed by Kugelrohr distillation
8. customthe crude product purified by column chromatography on silica gel

ORDレコード

ord-cf4b31d2f93941109cf24629b94e2a78

出典データセット

uspto-grants-2002_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06458951B2